TY - JOUR
T1 - Sleep and serotonin modulate paracapsular nitric oxide synthase expressing neurons of the amygdale
JF - eneuro
JO - eneuro
M3 - 10.1523/ENEURO.0177-16.2016
AU - Bocchio, Marco
AU - Fisher, Simon P
AU - Unal, Gunes
AU - Ellender, Tommas J
AU - Vyazovskiy, Vladyslav V
AU - Capogna, Marco
Y1 - 2016/09/26
UR - http://eneuro.org/content/early/2016/09/26/ENEURO.0177-16.2016.abstract
N2 - Unraveling the roles of distinct neuron types is a fundamental challenge to understand brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons is only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). These cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performing ex vivo patch clamp recordings from nNOS+ neurons in Nos1-CreER;Ai9 mice, we observed that nNOS+ neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS+ neurons are activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin (5-HT) neurons, which are involved in sleep-wake regulation, innervate nNOS+ neurons. Bath application of 5-HT hyperpolarizes nNOS+ neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS+ cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links between mood, sleep deprivation and 5-HT, the recruitment of paracapsular nNOS+ neurons following high sleep pressure may represent an important mechanism in emotional regulation.Significance Statement: Understanding the function of GABAergic neurons of the amygdala can greatly improve our knowledge of the cellular underpinnings of emotional behavior and improve therapies for psychiatric disorders. Here we report a novel GABAergic neuron type of the BLA that displays high levels of neuronal nitric oxide synthase. This neuron type shows high or low early gene expression during sleep or wakefulness, respectively. Our data suggest that reduced recruitment of these cells during sleep deprivation could originate, at least in part, from their inhibition by 5-HT, which is preferentially released during wakefulness but not during sleep. This work provides an important link between a specific GABAergic cell type of the amygdala, a wake-promoting neuromodulator and the sleep-wake cycle.
ER -